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L-citrulline is one of the three main amino acids in the Urea cycle (along with Arginine and Ornithine. It is found in high amounts in watermelon and some other citrus fruits.
Supplementing with L-Citrulline is usually preferred to the other two amino acids in the urea cycle for nitric oxide related purposes (the muscle pump) as it has greater intestinal uptake and passes the liver, going straight to the muscles.
Once it passes the liver and intestines, it goes to the kidneys to be turned into arginine. Because of this, most of the benefits on the Arginine page can also be attributed to Citrulline; albeit with different dosages and a grain of salt in application.
Things to Know
Also Known As
L-Citrulline, Stimol (Brand Name)
How to Take (recommended dosage, active amounts, other details)
Benefits have been seen in humans with doses of 6-8g before exercise.
Superloading may run the risk of reduced blood pressure, and would be relatively expensive.
1. Natural Sources
L-Citrulline is a non-protein amino acid compound, and unlike L-Arginine it is not widely present in all proteins. It is highest in watermelon and averages about 2.1mg/g wet weight, although absolute numbers varied. Eating watermelon actually can increase Citrulline and Arginine levels (the latter of which is most likely vicariously through citrulline), and 3.3 kilograms of watermelon can raise serum arginine levels the same as 10g of supplemental L-Arginine.
2. Intestinal Absorption
L-Citrulline is taken up to a much greater degree in the gut than its counterpart L-Arginine, and results in a higher plasma level of L-Arginine via the Arginine/Ornithine/Citrulline cycle. It is absorbed through numerous sodium-dependent transporters.
3. Usage in Exercise
Citrulline, when supplemented at dosages around 250mg/kg bodyweight, has been implicated in increasing anaerobic performance in rats. Aerobic performance has also been increased (in humans) at dosages of 6g/day and anaerobic performance at 8g a day.
The mechanism of which Citrulline exerts its benefits is via aiding in ammonia detoxification. Ammonia is a byproduct from muscle metabolism during exercise (from usage of ATP) and can inhibit the conversion of Pyruvate to Acetyl-CoA through activation of the phosphofructokinase enzyme, which causes a shift to lactate production and less Ca2+ release from the sarcoplasmic reticulum of muscles (via declining pH) and thus less contractility.
Citrulline, via Arginine and Nitric Oxide synthase activity, reduces the oxygen cost of muscle processes and delays this process and enhances performance. It is implicated at increasing ATP as well as phosphocreatine recovery rates during exercise and delaying time to exhaustion.
4. Erectile Dysfunction
Supplementing 1.5g per day of Citrulline helped improved Erectile Dysfunction in men with ED
5. Tolerance and safety
Citrulline appears to be well-tolerated by rats in doses up to 3g/kg bodyweight. No direct toxicity studies have been run on Citrulline at this moment in time, but the page on Arginine may give some guidance due to citrulline acting vicariously through arginine.
Scientific Support & Reference Citations
1. Rimando AM, Perkins-Veazie PM. Determination of citrulline in watermelon rind. J Chromatogr A. (2005)
2. Mandel H, et al. Elevated plasma citrulline and arginine due to consumption of Citrullus vulgaris (watermelon). J Inherit Metab Dis. (2005)
3. Tangphao O, et al. Pharmacokinetics of intravenous and oral L-arginine in normal volunteers. Br J Clin Pharmacol. (1999)
1. Curis E, Crenn P, Cynober L. Citrulline and the gut. Curr Opin Clin Nutr Metab Care. (2007)
1. Bahri S, et al. Mechanisms and kinetics of citrulline uptake in a model of human intestinal epithelial cells. Clin Nutr. (2008)
2. Takeda K, et al. Effects of citrulline supplementation on fatigue and exercise performance in mice. J Nutr Sci Vitaminol (Tokyo). (2011)
3. Giannesini B, et al. Citrulline malate supplementation increases muscle efficiency in rat skeletal muscle. Eur J Pharmacol. (2011)
4. Bendahan D, et al. Citrulline/malate promotes aerobic energy production in human exercising muscle. Br J Sports Med. (2002)
5. Pérez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res. (2010)
1. Ammonia Production in Muscle and other Tissues: the Purine Nucleotide Cycle
2. Regulation of the urea cycle and TCA cycle by ammonia
1. Fitts RH, Balog EM. Effect of intracellular and extracellular ion changes on E-C coupling and skeletal muscle fatigue. Acta Physiol Scand. (1996)
2. Merry TL, Lynch GS, McConell GK. Downstream mechanisms of nitric oxide-mediated skeletal muscle glucose uptake during contraction. Am J Physiol Regul Integr Comp Physiol. (2010)
3. Álvares TS, et al. L-Arginine as a potential ergogenic aid in healthy subjects. Sports Med. (2011)
4. Bailey SJ, et al. Acute L-arginine supplementation reduces the O2 cost of moderate-intensity exercise and enhances high-intensity exercise tolerance. J Appl Physiol. (2010)
1. Oral L-Citrulline Supplementation Improves Erection Hardness in Men With Mild Erectile Dysfunction
(Common misspellings for Citrulline include citruline, citrulllin, citrulin)
(Common phrases used by users for this page include which is better l arginine or l citrulline for muscle pump, l.citrulline dosage, l-citrulline nih erection, is l-citrulline better than ornithine, citrulline is good or bad, citrullin high)
L-Citrulline is one of the three amino acids in the Urea cycle alongside L-Arginine and L-Ornithine; it turns into L-Arginine after absorption and being sent to the kidneys, so it is actually a better method of getting supplemental L-Arginine into the blood rather than L-Arginine itself
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